Project 4, led by Drs. Lynn Matrisian and Wellington Pham, focuses on developing optical beacons and MRIcontrast agents for the in vivo detection of tumor-associated metalloproteinase activity as a novel mechanismto monitor response to tumor therapy. Members of the matrix metalloproteinase (MMP) family are implicated inthe matrix degradation associated with cancer invasion. There is substantial literature indicating theinvolvement of specific MMP family members in specific cellular processes related to cancer, including theactivation of growth factors, angiogenesis, infiltration of inflammatory cells, and invasion. These investigatorspropose to take advantage of this knowledge to devise a series of non-invasive in vivo imaging reagents thatwill probe the proteolytic status of a tumor to aid in treatment decisions, and rapidly assess the response tostandard and targeted cancer chemotherapies. Dr. Pham, a chemist by training, brings extensive experiencewith the design and synthesis of optical probes for proteolytic activity, and Dr. Matrisian, a cancer biologist, hasextensive experience exploring the role of metalloproteinases in mouse models of cancer. Murine models ofbenign, malignant, and metastatic colorectal cancer will be used in this project, and the response to cancertherapies directed at the epidermal growth factor (EGF) receptor axis will be tested in collaboration withprojects 1 and 3 of this ICMIC proposal.
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